Raff Laboratory

Location
Health Research Center
H4200

General Interests
Physiology, Endocrinology, Clinical Chemistry

Research Areas

Hypoxia is common with preterm birth and may lead to long-term effects on the adult hypothalamic-pituitary-adrenal (HPA) axis that are sexually dimorphic due to neonatal androgens. Although the adult rat adrenal does not express appreciable CYP17 activity, the neonatal rat adrenal may synthesize androgens that could be a critical local factor in the development of adrenal function. We evaluated these phenomena by pretreating the neonatal rats on postnatal days (PD) 1, 6, 13, 20 with flutamide (a non-steroidal androgen receptor antagonist) at a standard or a high-dose (10 mg/kg or 50 mg/kg) compared to vehicle control. One day later, neonatal rats were exposed to acute hypoxia and blood was sampled. Our studies suggest that neonatal androgens play a role in regulation of adrenal function that is sexually dimorphic and changes during early development.

Premature birth is a major public health problem worldwide and can lead to transient adrenal insufficiency. The stress of premature birth includes the inability to control blood glucose and maintain normal oxygenation leading to hypoxia. Corticosteroid administration enhances surfactant production and improves oxygenation in preterm humans. However, corticosteroids can also have negative consequences. We have validated a rat model of separation and hypoxia on post-natal day (PD) 2 that emulates the stress and treatment of hypoxia in the preterm human infant. We hypothesized that the role of endogenous glucocorticoids in our neonatal rat model of preterm birth can be evaluated using the novel selective glucocorticoid receptor (GR) antagonist CORT113176 (Corcept) which is devoid of progesterone receptor effects. The differential effects of CORT113176 based on age and target tissue indicate that GR regulation changes in early development in our animal model of human prematurity. These findings may have significant implications in the treatment of hypoxia and transient adrenal insufficiency in the preterm infant as well as give insight into the nuances of the control of glucocorticoid receptor function.

Late-night salivary cortisol (LNSC) measured by enzyme immunoassay (EIA) is established as a reliable screening test and recommended as a first-line test for Cushing’s syndrome. However, liquid chromatography-tandem mass spectrometry (LCMS), validated to measure salivary cortisol (F) and cortisone (E), has been proposed to be superior diagnostically as well as helpful in detecting saliva contaminated with topical hydrocortisone (i.e. cortisol). So far we have measured EIA-F, LCMS-F, and LCMS-E in 913 consecutive late-night saliva samples from patients suspected of Cushing’s syndrome. EIA-F appears to be superior to LCMS-F in identifying CD patients with milder hypercortisolism using established diagnostic cutoffs. Neither LCMS-E nor F/E ratio improved the diagnostic sensitivity in newly diagnosed CD or persistent/recurrent CD after pituitary surgery. We suggest that late-night salivary cortisol measured by EIA provides the best sensitivity for CD diagnosis.

Current Members

Ashley Gehrand, MS

Research Associate

Jonathan Phillips, BS

Research Associate

Santiago Rolon

M3 Medical Student
Pathway Research Project

Kyle Welhouse

M2 Medical Student
Pathway Research Project

Molly Murray

M1 Medical Student
Pathway Student

Josh Kannakeril, MD

Clinical Endocrine Fellow

Alumni/Former Trainees

Clinical Fellows (Research)

Thomas P. Segerson, MD 鈥� Research Fellow
Victor O. Waters, MD 鈥� Critical Care Fellow
Santo J. Diaz, MD 鈥� Critical Care Fellow
Manoj H. Majmudar, MD 鈥� Critical Care Fellow
Robert C. Brickner, MD 鈥� Endocrine Metabolic Fellow
Pennapa Chan, MD 鈥� Endocrine-Metabolic Fellow
Scott Brock, MD 鈥� Endocrine-Metabolic Fellow
Sandra L. Ettema, MD, PhD, CCC-SLP 鈥� Otolaryngology Resident
Vidya Kidambi, MD 鈥� Endocrine-Metabolic Fellow
Ty Carroll, MD 鈥� Endocrine-Metabolic Fellow
Jay Mepani, MD-Endocrine-Metabolic Fellow
Michael Einstein, MD 鈥� GI Fellow
Giovanna Caprirolo, MD 鈥� Pediatric Critical Care Fellow
Mohamed Tahsin Jouhari, MD 鈥� Pediatric Critical Care Fellow
Neil Reisinger, MD 鈥� Chief Medical Resident
Nebiyu Biru, MD 鈥� Chief Medical Resident
Satyanisth Agrawal, MD 鈥� GI Fellow
Brian Rajca, MD 鈥� GI Fellow
Julia Leo, MD 鈥� GI Fellow
Veena Kumaravel, MD 鈥� GI Fellow
Jonathan Fahler, MD 鈥� GI Fellow

Post Doctoral Research Fellow

Paula. E. Papanek, PhD

Graduate Students

Eric D. Bruder, MS 鈥� University of Wisconsin, Milwaukee

Medical Student Research Trainees 鈥� 星空无限传媒

Timothy P. Roarty
Maryam Ivanoff
Steven C. Griffen
Saeid Kohandarvish
Mark H. Rossing
Sandra K. Doepker
Pedro Lucero
Anne Nagler
Jody VanHoof
Karl Johnson (Clinician Scientist Pathway Advisor, 2011-2014; T35 Training Grant from National Heart, Lung, Blood Institute (NHLBI))
Jonathan Bodager (Clinical Scientist Pathway Advisor, 2013-2016)
Nasha Nensey (Physician Scientist 鈥� Molecular and Cellular Research Pathway Advisor, 2014-2017)
Adam Goldenberg (Physician Scientist 鈥� Molecular and Cellular Research Pathway); Advisor, 2016-2019; T35 Training Grant from the National Heart, Lung, Blood Institute (NHLBI)
Christine Huyhn (Quality Improvement and Patient Safety Pathway); Research Advisor 2017, Dr. Michael J. Dunn Medical Student Summer Research Training Fellowship)

Undergraduate Summer Trainees

A. Joseph Tector, III 鈥� Indiana University
Edward Stauber (1997 Endocrine Society Student Research Fellow) 鈥� University of Wisconsin
Genevieve Schmitt 鈥� College of the Holy Cross
Seth Auger 鈥� University of Dayton
Judson Werner 鈥� University of Wisconsin
Michael Patrick Kehoe 鈥� University of Wisconsin
Jonathan Klinger 鈥� Marquette University
John P. Tucker 鈥� University of Wisconsin
Jennifer Taylor 鈥� Northwestern University
Michael Nord 鈥� University of Minnesota
Kimberli Kamer 鈥� University of Wisconsin
Mitchell Guenther 鈥� Lawrence University
Christopher Wean 鈥� Renssalaer Polytechnic Institute
Kathan Chintamaneni 鈥� Washington University of St. Louis
Kristin Prewitt 鈥� University of Wisconsin
Thomas Gessert 鈥� University of Wisconsin
Mack Jablonski 鈥� Lawrence University
Cole Leonovicz 鈥� University of Miami
Emily Waples 鈥� Duke University
Minhal Gardezi 鈥� Wellesley College
Maya Guenther 鈥� Lawrence University
Matthew Schulgit 鈥� University of Wisconsin
Hana Siddiqui 鈥� University of Wisconsin

(Raff H, Hainsworth KR, Woyach VL, Weihrauch D, Wang X, Dean C.) Am J Physiol Regul Integr Comp Physiol. 2024 Aug 01;327(2):R123-R132 PMID: 38780441 SCOPUS ID: 2-s2.0-85198683818 05/23/2024
(DeGroot A, Huber DL, Leddy JJ, Raff H, McCrea MA, Johnson BD, Nelson LD.) PM R. 2024 Aug;16(8):826-835 PMID: 38411367 PMCID: PMC11323219 SCOPUS ID: 2-s2.0-85186544012 02/27/2024
(Raff H.) J Clin Endocrinol Metab. 2024 Jul 12;109(8):e1669-e1670 PMID: 38214548 SCOPUS ID: 2-s2.0-85198681504 01/12/2024
(Lawton SB, Grobe CC, Reho JJ, Raff H, Thulin JD, Jensen ES, Burnett CM, Segar JL, Grobe JL.) J Am Assoc Lab Anim Sci. 2024 Mar 01;63(2):190-200 PMID: 38191147 PMCID: PMC11022944 SCOPUS ID: 2-s2.0-85192114074 01/09/2024
(Raff H.) J Endocr Soc. 2024 Jan 16;8(3):bvae007 PMID: 38292594 PMCID: PMC10825827 01/31/2024
(Raff H.) Journal of the Endocrine Society. 1 March 2024;8(3) SCOPUS ID: 2-s2.0-85184025030 03/01/2024
(Olsen CM, Glaeser BL, Szabo A, Raff H, Everson CA.) Physiol Behav. 2023 Dec 01;272:114372 PMID: 37805135 PMCID: PMC10841994 SCOPUS ID: 2-s2.0-85173957688 10/08/2023
(Wagner VA, Holl KL, Clark KC, Reho JJ, Lehmler HJ, Wang K, Grobe JL, Dwinell MR, Raff H, Kwitek AE.) Endocrinology. 2023 Nov 02;164(12) PMID: 37882530 PMCID: PMC10637104 SCOPUS ID: 2-s2.0-85176509096 10/26/2023
(Findling JW, Raff H.) J Endocr Soc. 2023 Jul 03;7(8):bvad087 PMID: 37440963 PMCID: PMC10334485 07/13/2023
(Wagner VA, Holl KL, Clark KC, Reho JJ, Dwinell MR, Lehmler HJ, Raff H, Grobe JL, Kwitek AE.) Toxicol Sci. 2023 Jun 28;194(1):84-100 PMID: 37191987 PMCID: PMC10306406 SCOPUS ID: 2-s2.0-85164065947 05/16/2023
(Raff H, Zhang CD.) NEJM Evid. 2023 Feb;2(2):EVIDe2200306 PMID: 38320042 02/06/2024
(Surani A, Carroll TB, Javorsky BR, Raff H, Findling JW.) Front Endocrinol (Lausanne). 2023;14:1199091 PMID: 37409223 PMCID: PMC10319132 07/06/2023

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